Detection of thirty novel FBN1 mutations in patients with Marfan syndrome or a related fibrillinopathy.


:Marfan syndrome (MFS) is a disorder of the extracellular matrix caused by mutations in the gene encoding fibrillin-1 (FBN1). Recent studies have illustrated the variability in disease severity and clinical manifestations of MFS. Useful genotype-phenotype correlations have been slow to emerge. We screened 57 unrelated patients with MFS or a Marfan-like phenotype using a combination of SSCP and/or DHPLC. We detected 49 different FBN1 mutations, 30 (62%) of which were novel. The mutations comprised 38 substitutions (78%), 10 deletions (20%), and one duplication (2%). There were 28 missense (57%), nine frameshift (18%), eight splice site (16%), and four nonsense mutations (8 %). Genotype-phenotype analysis revealed that patients with an identified FBN1 mutation were more likely to have ectopia lentis and cardiovascular complications compared to those without an identifiable mutation (relative risks of 4.6 and 1.9, respectively). Ectopia lentis was also found to be more prevalent in patients whose mutations involved a cysteine substitution (relative risk 1.6) and less prevalent in those with premature termination mutations (relative risk 0.4). In our hands, we achieved 93% mutation detection for DHPLC analysis of patients who fulfilled the Ghent criteria. Further analysis of detailed clinical information and mutation data may help to anticipate the clinical consequences of specific FBN1 mutations.


Hum Mutat


Human mutation


Biggin A,Holman K,Brett M,Bennetts B,Adès L





Has Abstract


2004-01-01 00:00:00












  • Classification of Genes: Standardized Clinical Validity Assessment of Gene-Disease Associations Aids Diagnostic Exome Analysis and Reclassifications.

    abstract::Ascertaining a diagnosis through exome sequencing can provide potential benefits to patients, insurance companies, and the healthcare system. Yet, as diagnostic sequencing is increasingly employed, vast amounts of human genetic data are produced that need careful curation. We discuss methods for accurately assessing t...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Smith ED,Radtke K,Rossi M,Shinde DN,Darabi S,El-Khechen D,Powis Z,Helbig K,Waller K,Grange DK,Tang S,Farwell Hagman KD

    更新日期:2017-05-01 00:00:00

  • Identification of a novel NOG gene mutation (P35S) in an Italian family with symphalangism.

    abstract::Symphalangism (SYM or SYM1) is an autosomal dominant disorder characterized by multiple joint fusions. The disease is caused by mutations of the NOG gene, that maps to chromosome 17q22. So far, only six independent NOG mutations have been identified. We have analysed an Italian family in which father and son had bilat...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Mangino M,Flex E,Digilio MC,Giannotti A,Dallapiccola B

    更新日期:2002-03-01 00:00:00

  • A mild neurofibromatosis type 1 phenotype produced by the combination of the benign nature of a leaky NF1-splice mutation and the presence of a complex mosaicism.

    abstract::Here we analyze the genetic and molecular basis responsible for a very benign phenotype observed in an NF1 patient. Quantification of cells carrying the NF1 mutation in different samples derived from the three embryonic layers revealed mosaicism. Furthermore, the construction of a minigene with patient's mutation (c.3...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Fernández-Rodríguez J,Castellsagué J,Benito L,Benavente Y,Capellá G,Blanco I,Serra E,Lázaro C

    更新日期:2011-07-01 00:00:00

  • Thermal instability of compound variants of carnitine palmitoyltransferase II and impaired mitochondrial fuel utilization in influenza-associated encephalopathy.

    abstract::Influenza-associated encephalopathy (IAE) is characterized by persistent high fever, febrile convulsions, severe brain edema, and high mortality in otherwise apparently healthy individuals. We have reported that a large proportion of patients suffering from disabling or fatal IAE, with transiently elevated serum acylc...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Yao D,Mizuguchi H,Yamaguchi M,Yamada H,Chida J,Shikata K,Kido H

    更新日期:2008-05-01 00:00:00

  • Multiple LRRK2 variants modulate risk of Parkinson disease: a Chinese multicenter study.

    abstract::We and others found two polymorphic LRRK2 (leucine-rich repeat kinase 2) variants (rs34778348:G>A; p.G2385R and rs33949390:G>C; p.R1628P) associated with Parkinson disease (PD) among Chinese patients, but the common worldwide rs34637584:G>A; p.G2019S mutation, was absent. Focusing exclusively on Han Chinese, we first ...

    journal_title:Human mutation

    pub_type: 杂志文章,多中心研究


    authors: Tan EK,Peng R,Teo YY,Tan LC,Angeles D,Ho P,Chen ML,Lin CH,Mao XY,Chang XL,Prakash KM,Liu JJ,Au WL,Le WD,Jankovic J,Burgunder JM,Zhao Y,Wu RM

    更新日期:2010-05-01 00:00:00

  • Comprehensive clinical and molecular assessment of 32 probands with congenital contractural arachnodactyly: report of 14 novel mutations and review of the literature.

    abstract::Beals-Hecht syndrome or congenital contractural arachnodactyly (CCA) is a rare, autosomal dominant connective tissue disorder characterized by crumpled ears, arachnodactyly, contractures, and scoliosis. Recent reports also mention aortic root dilatation, a finding previously thought to differentiate the condition from...

    journal_title:Human mutation

    pub_type: 杂志文章,评审


    authors: Callewaert BL,Loeys BL,Ficcadenti A,Vermeer S,Landgren M,Kroes HY,Yaron Y,Pope M,Foulds N,Boute O,Galán F,Kingston H,Van der Aa N,Salcedo I,Swinkels ME,Wallgren-Pettersson C,Gabrielli O,De Backer J,Coucke PJ,De Paep

    更新日期:2009-03-01 00:00:00

  • Mutation nomenclature in practice: findings and recommendations from the cystic fibrosis external quality assessment scheme.

    abstract::Currently, two nomenclature systems are in use to describe sequence variants for cystic fibrosis: the established traditional nomenclature system and the more recent Human Genome Variation Society (HGVS) nomenclature system. We have evaluated the use of both systems in the laboratory reports of 217 participants in the...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Berwouts S,Morris MA,Girodon E,Schwarz M,Stuhrmann M,Dequeker E

    更新日期:2011-11-01 00:00:00

  • Molecular diagnosis of inherited disorders: lessons from hemoglobinopathies.

    abstract::Hemoglobinopathies constitute a major health problem worldwide, with a high carrier frequency, particularly in certain regions where malaria has been endemic. These disorders are characterized by a vast clinical and hematological phenotypic heterogeneity. Over 1,200 different genetic alterations that affect the DNA se...

    journal_title:Human mutation

    pub_type: 杂志文章,评审


    authors: Patrinos GP,Kollia P,Papadakis MN

    更新日期:2005-11-01 00:00:00

  • Further delineation of Malan syndrome.

    abstract::Malan syndrome is an overgrowth disorder described in a limited number of individuals. We aim to delineate the entity by studying a large group of affected individuals. We gathered data on 45 affected individuals with a molecularly confirmed diagnosis through an international collaboration and compared data to the 35 ...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Priolo M,Schanze D,Tatton-Brown K,Mulder PA,Tenorio J,Kooblall K,Acero IH,Alkuraya FS,Arias P,Bernardini L,Bijlsma EK,Cole T,Coubes C,Dapia I,Davies S,Di Donato N,Elcioglu NH,Fahrner JA,Foster A,González NG,Huber

    更新日期:2018-09-01 00:00:00

  • A nationwide genetic analysis of inherited retinal diseases in Israel as assessed by the Israeli inherited retinal disease consortium (IIRDC).

    abstract::Inherited retinal diseases (IRDs) cause visual loss due to dysfunction or progressive degeneration of photoreceptors. These diseases show marked phenotypic and genetic heterogeneity. The Israeli IRD consortium (IIRDC) was established in 2013 with the goal of performing clinical and genetic mapping of the majority of I...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Sharon D,Ben-Yosef T,Goldenberg-Cohen N,Pras E,Gradstein L,Soudry S,Mezer E,Zur D,Abbasi AH,Zeitz C,Cremers FPM,Khan MI,Levy J,Rotenstreich Y,Birk OS,Ehrenberg M,Leibu R,Newman H,Shomron N,Banin E,Perlman I

    更新日期:2020-01-01 00:00:00

  • Molecular Genetic Characterization of 151 Mut-Type Methylmalonic Aciduria Patients and Identification of 41 Novel Mutations in MUT.

    abstract::Isolated methylmalonic aciduria (MMA) is an autosomal-recessive disorder of propionate metabolism that is most commonly caused by mutations in the methylmalonyl-CoA mutase (MUT) gene (mut-type MMA). We investigated a cohort of 151 patients, classifying 114 patients as mut(0) and 32 as mut(-) (five not defined). As per...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Forny P,Schnellmann AS,Buerer C,Lutz S,Fowler B,Froese DS,Baumgartner MR

    更新日期:2016-08-01 00:00:00

  • Allelic imbalance (AI) identifies novel tissue-specific cis-regulatory variation for human UGT2B15.

    abstract::Allelic imbalance (AI) is a powerful tool to identify cis-regulatory variation for gene expression. UGT2B15 is an important enzyme involved in the metabolism of multiple endobiotics and xenobiotics. In this study, we measured the relative expression of two alleles at this gene by using SNP rs1902023:G>T. An excess of ...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Sun C,Southard C,Witonsky DB,Olopade OI,Di Rienzo A

    更新日期:2010-01-01 00:00:00

  • Enzymatic mutation detection (EMD) of novel mutations (R565X and R1523X) in the FBN1 gene of patients with Marfan syndrome using T4 endonuclease VII.

    abstract::The Enzymatic Mutation Detection (EMDtrade mark) method is a streamlined and improved version of the original Enzymatic Cleavage of Mismatch (EMC) method. EMD is a fully homogeneous, rapid four step procedure that allows for detection and localization of mismatched or unmatched nucleotides within heteroduplex DNA. To ...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Youil R,Toner TJ,Bull E,Bailey AL,Earl CD,Dietz HC,Montgomery RA

    更新日期:2000-07-01 00:00:00

  • Genetic diversity from a limited repertoire of mutations on different common allelic backgrounds: alpha 1-antitrypsin deficiency variant Pduarte.

    abstract::alpha 1-Antitrypsin (alpha 1AT) is one of the most polymorphic gene loci in the human genome. alpha 1AT variants are typically identified by their migration position in an isoelectric focusing gel at pH 4-5. Heterogeneity of the isoelectric point of alpha 1AT variants, hence variant migration, most often results from ...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Hildesheim J,Kinsley G,Bissell M,Pierce J,Brantly M

    更新日期:1993-01-01 00:00:00

  • Screening of ARHSP-TCC patients expands the spectrum of SPG11 mutations and includes a large scale gene deletion.

    abstract::Autosomal recessive spastic paraplegia with thinning of corpus callosum (ARHSP-TCC) is a complex form of HSP initially described in Japan but subsequently reported to have a worldwide distribution with a particular high frequency in multiple families from the Mediterranean basin. We recently showed that ARHSP-TCC is c...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Denora PS,Schlesinger D,Casali C,Kok F,Tessa A,Boukhris A,Azzedine H,Dotti MT,Bruno C,Truchetto J,Biancheri R,Fedirko E,Di Rocco M,Bueno C,Malandrini A,Battini R,Sickl E,de Leva MF,Boespflug-Tanguy O,Silvestri G,S

    更新日期:2009-03-01 00:00:00

  • An automated procedure to identify biomedical articles that contain cancer-associated gene variants.

    abstract::The proliferation of biomedical literature makes it increasingly difficult for researchers to find and manage relevant information. However, identifying research articles containing mutation data, a requisite first step in integrating large and complex mutation data sets, is currently tedious, time-consuming and impre...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: McDonald R,Scott Winters R,Ankuda CK,Murphy JA,Rogers AE,Pereira F,Greenblatt MS,White PS

    更新日期:2006-09-01 00:00:00

  • A homozygous GJA1 gene mutation causes a Hallermann-Streiff/ODDD spectrum phenotype.

    abstract::Oculodentodigital dysplasia (ODDD) and Hallermann-Streiff syndrome (HSS) share several clinical characteristics. However, while ODDD is a dominantly inherited disorder due to mutations in the connexin 43 gene GJA1, the inheritance pattern of the HSS syndrome is still debated. Overlapping phenotypes have been described...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Pizzuti A,Flex E,Mingarelli R,Salpietro C,Zelante L,Dallapiccola B

    更新日期:2004-03-01 00:00:00

  • Assessment of predicted enzymatic activity of α-N-acetylglucosaminidase variants of unknown significance for CAGI 2016.

    abstract::The NAGLU challenge of the fourth edition of the Critical Assessment of Genome Interpretation experiment (CAGI4) in 2016, invited participants to predict the impact of variants of unknown significance (VUS) on the enzymatic activity of the lysosomal hydrolase α-N-acetylglucosaminidase (NAGLU). Deficiencies in NAGLU ac...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Clark WT,Kasak L,Bakolitsa C,Hu Z,Andreoletti G,Babbi G,Bromberg Y,Casadio R,Dunbrack R,Folkman L,Ford CT,Jones D,Katsonis P,Kundu K,Lichtarge O,Martelli PL,Mooney SD,Nodzak C,Pal LR,Radivojac P,Savojardo C,Shi

    更新日期:2019-09-01 00:00:00

  • Molecular genetics of familial hypercholesterolemia in Spain: Ten novel LDLR mutations and population analysis.

    abstract::Mutations underlying FH in Spain are largely unknown because only a few and limited surveys have been carried out on Spanish FH patients up to now. To gain information on this issue, we have analysed a group of 113 unrelated Spanish FH patients from an eastern area of Spain (Valencian Community). We have screened the ...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: García-García AB,Real JT,Puig O,Cebolla E,Marín-García P,Martínez Ferrandis JI,García-Sogo M,Civera M,Ascaso JF,Carmena R,Armengod ME,Chaves FJ

    更新日期:2001-11-01 00:00:00

  • The distribution of constitutional and somatic mutations in the neurofibromatosis 2 gene.

    abstract::Constitutional heterozygous inactivating mutations in the neurofibromatosis 2 (NF2) tumor suppressor gene cause the autosomal dominant disease NF2, and biallelic inactivating somatic NF2 mutations are found in a high proportion of unilateral sporadic vestibular schwannoma (USVS) and sporadic meningioma. We surveyed th...

    journal_title:Human mutation

    pub_type: 杂志文章,评审


    authors: Baser ME,Contributors to the International NF2 Mutation Database.

    更新日期:2006-04-01 00:00:00

  • Mass allele detection (MAD) of rare 5-HT1A structural variants with allele-specific amplification and electrochemiluminescent detection.

    abstract::A strategy is described that exploits allele-specific amplification (ASA-PCR) and electrochemiluminescence (ECL) detection technology to rapidly and cheaply screen large numbers of DNAs arranged in pooled matrices in order to identify individual nucleotide sequence variants. To demonstrate this strategy, a large genom...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Bergen A,Wang CY,Nakhai B,Goldman D

    更新日期:1996-01-01 00:00:00

  • Quantitative allele-specific PCR: demonstration of age-associated accumulation in human tissues of the A-->G mutation at nucleotide 3243 in mitochondrial DNA.

    abstract::We have developed an improved allele-specific polymerase chain reaction (AS-PCR) procedure that can selectively amplify mutant DNA sequences (which differ from the normal sequences by a single base pair) in the presence of large excess of normal sequences. We applied this procedure to quantification of mutant molecule...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Liu VW,Zhang C,Linnane AW,Nagley P

    更新日期:1997-01-01 00:00:00

  • HGVS Nomenclature in Practice: An Example from the United Kingdom National External Quality Assessment Scheme.

    abstract::The recommendations for the description of sequence variants from the Human Genome Variation Society (HGVS) were published in 2000. Over the years, the recommendations became widely adopted, especially in human clinical genetics and DNA laboratory reporting. As part of a testing scheme performed by the United Kingdom ...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Deans ZC,Fairley JA,den Dunnen JT,Clark C

    更新日期:2016-06-01 00:00:00

  • Molecular defects in human carbamoy phosphate synthetase I: mutational spectrum, diagnostic and protein structure considerations.

    abstract::Deficiency of carbamoyl phosphate synthetase I (CPSI) results in hyperammonemia ranging from neonatally lethal to environmentally induced adult-onset disease. Over 24 years, analysis of tissue and DNA samples from 205 unrelated individuals diagnosed with CPSI deficiency (CPSID) detected 192 unique CPS1 gene changes, o...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Häberle J,Shchelochkov OA,Wang J,Katsonis P,Hall L,Reiss S,Eeds A,Willis A,Yadav M,Summar S,Urea Cycle Disorders Consortium.,Lichtarge O,Rubio V,Wong LJ,Summar M

    更新日期:2011-06-01 00:00:00

  • The molecular basis of X-linked deafness type 3 (DFN3) in two sporadic cases: identification of a somatic mosaicism for a POU3F4 missense mutation.

    abstract::We have investigated two unrelated males with X-linked deafness type 3 (DFN3) for mutations in the POU3F4 gene. In one patient, we observed a mutation that is predicted to result in an Arg330Ser amino acid substitution. In another DFN3 patient, a somatic mosaicism for an Arg323Gly amino acid substitution was found. Th...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: de Kok YJ,Cremers CW,Ropers HH,Cremers FP

    更新日期:1997-01-01 00:00:00

  • Discovery of genetic profiles impacting response to chemotherapy: application to gemcitabine.

    abstract::Chemotherapy is a major treatment modality for individuals affected by cancer. Currently, a number of genome-based technologies are being adopted to identify genes associated with drug response; however, large-scale genetic association applications are still limited. Here we describe a novel strategy based on the gene...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Jarjanazi H,Kiefer J,Savas S,Briollais L,Tuzmen S,Pabalan N,Ibrahim-Zada I,Mousses S,Ozcelik H

    更新日期:2008-04-01 00:00:00

  • Two independent retrotransposon insertions at the same site within the coding region of BTK.

    abstract::Insertion of endogenous retrotransposon sequences accounts for approximately 0.2% of disease causing mutations. These insertions are mediated by the reverse transcriptase and endonuclease activity of long interspersed nucleotide (LINE-1) elements. The factors that control the target site selection in insertional mutag...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Conley ME,Partain JD,Norland SM,Shurtleff SA,Kazazian HH Jr

    更新日期:2005-03-01 00:00:00

  • Deletions removing the last exon of TACSTD1 constitute a distinct class of mutations predisposing to Lynch syndrome.

    abstract::Several different genetic alterations in the etiology of Lynch syndrome (hereditary nonpolyposis colorectal cancer [HNPCC]) are known, mostly point mutations and genomic rearrangements in 1 of at least 3 mismatch-repair (MMR) genes. However, no susceptibility factor has yet been identified in a significant part (30-50...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Kovacs ME,Papp J,Szentirmay Z,Otto S,Olah E

    更新日期:2009-02-01 00:00:00

  • Microsatellite in the 3' untranslated region of human fibroblast growth factor 9 (FGF9) gene exhibits pleiotropic effect on modulating FGF9 protein expression.

    abstract::Fibroblast growth factor 9 (FGF9) is a member of secreted polypeptide families and involved in many important biological processes, including implantation and morphogenesis during embryogenesis and adult life. Recently, Fgf9-knockout mice exhibited male-to-female sex reversal, demonstrating a novel function for FGF9 i...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Chen TM,Kuo PL,Hsu CH,Tsai SJ,Chen MJ,Lin CW,Sun HS

    更新日期:2007-01-01 00:00:00

  • A dominant STIM1 mutation causes Stormorken syndrome.

    abstract::Stormorken syndrome is a rare autosomal-dominant disease with mild bleeding tendency, thrombocytopathy, thrombocytopenia, mild anemia, asplenia, tubular aggregate myopathy, miosis, headache, and ichthyosis. A heterozygous missense mutation in STIM1 exon 7 (c.910C>T; p.Arg304Trp) (NM_003156.3) was found to segregate wi...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Misceo D,Holmgren A,Louch WE,Holme PA,Mizobuchi M,Morales RJ,De Paula AM,Stray-Pedersen A,Lyle R,Dalhus B,Christensen G,Stormorken H,Tjønnfjord GE,Frengen E

    更新日期:2014-05-01 00:00:00